scholarly journals Molecular Targets and Associated Signaling Pathways of Jingshu Granules in Ovarian Cysts Based on Systemic Pharmacological Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jili Xu ◽  
Yincong Xu ◽  
Ye Zhu ◽  
Zhihui Li ◽  
Xiaoping Wang
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Targets ◽  
Young Female ◽  
Female Rats ◽  
Ovarian Cysts ◽  
Receptor Signaling ◽  
Active Ingredients ◽  
Protein Targets ◽  
Receptor Signaling Pathway

Background. More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis. Methods. Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts. Results. In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained. Conclusion. Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.

scholarly journals Transcriptome Analysis for Genes Associated with Small Ruminant Lentiviruses Infection in Goats of Carpathian Breed

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2054
Author(s):  
Monika Olech ◽  
Katarzyna Ropka-Molik ◽  
Tomasz Szmatoła ◽  
Katarzyna Piórkowska ◽  
Jacek Kuźmak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Proviral Load ◽  
Cytokine Production ◽  
Small Ruminant ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Receptor Signaling Pathway

Small ruminant lentiviruses (SRLV) are economically important viral pathogens of sheep and goats. SRLV infection may interfere in the innate and adaptive immunity of the host, and genes associated with resistance or susceptibility to infection with SRLV have not been fully recognized. The presence of animals with relatively high and low proviral load suggests that some host factors are involved in the control of virus replication. To better understand the role of the genes involved in the host response to SRLV infection, RNA sequencing (RNA-seq) method was used to compare whole gene expression profiles in goats carrying both a high (HPL) and low (LPL) proviral load of SRLV and uninfected animals. Data enabled the identification of 1130 significant differentially expressed genes (DEGs) between control and LPL groups: 411 between control and HPL groups and 1434 DEGs between HPL and LPL groups. DEGs detected between the control group and groups with a proviral load were found to be significantly enriched in several gene ontology (GO) terms, including an integral component of membrane, extracellular region, response to growth factor, inflammatory and innate immune response, transmembrane signaling receptor activity, myeloid differentiation primary response gene 88 (MyD88)-dependent toll-like receptor signaling pathway as well as regulation of cytokine secretion. Our results also demonstrated significant deregulation of selected pathways in response to viral infection. The presence of SRLV proviral load in blood resulted in the modification of gene expression belonging to the toll-like receptor signaling pathway, the tumor necrosis factor (TNF) signaling pathway, the cytokine-cytokine receptor interaction, the phagosome, the Ras signaling pathway, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt) signaling pathway and rheumatoid arthritis. It is worth mentioning that the most predominant in all pathways were genes represented by toll-like receptors, tubulins, growth factors as well as interferon gamma receptors. DEGs detected between LPL and HPL groups were found to have significantly enriched regulation of signaling receptor activity, the response to toxic substances, nicotinamide adenine dinucleotide (NADH) dehydrogenase complex assembly, cytokine production, vesicle, and vacuole organization. In turn, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway tool classified DEGs that enrich molecular processes such as B and T-cell receptor signaling pathways, natural killer cell-mediated cytotoxicity, Fc gamma R-mediated phagocytosis, toll-like receptor signaling pathways, TNF, mammalian target of rapamycin (mTOR) signaling and forkhead box O (Foxo) signaling pathways, etc. Our data indicate that changes in SRLV proviral load induced altered expression of genes related to different biological processes such as immune response, inflammation, cell locomotion, and cytokine production. These findings provide significant insights into defense mechanisms against SRLV infection. Furthermore, these data can be useful to develop strategies against SRLV infection by selection of animals with reduced SRLV proviral concentration that may lead to a reduction in the spread of the virus.

scholarly journals Network Pharmacology-Based Study of Active Ingredients and Mechanisms of Compound Xuanju for Rheumatoid Arthritis

2020 ◽  
Vol 3 (10) ◽  
pp. 712-723
Author(s):  
Fuxue Meng ◽  
Xiaomai Tao ◽  
Longkuan Li ◽  
Xin Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Venn Diagram ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Akt Signaling Pathway ◽  
Active Ingredients ◽  
Receptor Signaling Pathway ◽  
Target Database

Objective: Compound Xuanju has good effects in treating rheumatoid arthritis (RA), but its composition is complex, and its active ingredients and mechanism have not been fully defined. In this study, the active ingredients and mechanism of compound Xuanju for the treatment of RA were explored through network pharmacological methods. Methods: TCMSP and TCMID, Pubmed, CNKI, Wanfang, and VIP databases were used to screen, select active pharmaceutical ingredients and targets; Drugbank disease target screening database, GeneCards database, Therapeutic The Target Database (TTD) database and DisGeNET database were used to collect RA  targets, and OmicShare was used to screen compound Xuanju and RA for common targets and construct a Venn diagram. A protein target database String was used to construct a common target interaction network. OmicShare mapping software builds a "drug-active ingredient-target" network and analyzes their associations. DAVID online software performs gene annotation (GO) and KEGG pathway enrichment analysis on key targets. Results: A total of 73 effective ingredients of compound Xuanju were obtained, and corresponding to 229 targets; 2337 targets for RA. 155 key targets for potential active ingredients of compound Xuanju predicted therapeutic effect of RA, the key targets map 55 active ingredients of compound Xuanju capsules. These targets mainly involve signaling pathways such as Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway acting on RA. Conclusion: Compound Xuanju may via its potential 55 active ingredients act on 155 targets to treat RA through Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, NF-κB signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. This study lays the theoretical basis for the widespread application of compound Xuanju in clinical practice.

scholarly journals Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

2020 ◽  
Author(s):  
Shijia Guo ◽  
Xinan Zhang ◽  
mingli Sun
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Signaling Proteins ◽  
Receptor Signaling ◽  
In Vivo Experiments ◽  
Receptor Signaling Pathway

Abstract Background Scutellarin was reported to exerted inhibitive effects on osteoarthritis, However, the detailed mechanisms remain unclear. In this study, we investigated underlying multi-target mechanisms of scutellarin against osteoarthritis by using network pharmacology analysis and molecular docking. Results Scutellarin exerted inhibitive effects on osteoarthritis by regulating the function of several new signaling pathways, such as TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway. Molecular docking analysis showed there was better interaction between scutellarin and several NF-kB signaling proteins, including NFKBIA, RELA and NFKB1. In addition, the results showed Pi-cation, Pi-donor-hydrogen and Pi-alkyl were the main forms of interaction between scutellarin and NFKB1 and NFKBIA, Pi-Pi T-shaped, Pi-alkyl and hydrogen bonding were the main forms of interaction between scutellarin and RELA. Conclusion Taken together, TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway were possible signaling pathways, NFKBIA, RELA and NFKB1were possible targets associated with the activities of scutellarin against osteoarthritis. However, it is imperative that these targets should be thoroughly verified by in vitro and in vivo experiments.

scholarly journals Immune Infiltration Characteristics of Related Receptor Signaling Pathways in Primary Sjögren’s Syndrome

2021 ◽  
Author(s):  
Lingling Wu ◽  
Huayun Ling ◽  
Hong Wang ◽  
Lijuan Qiu ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Primary Sjögren’S Syndrome ◽  
Receptor Signaling ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Immune Infiltration ◽  
Receptor Signaling Pathway

Abstract Background: Primary Sjögren’s Syndrome (pSS) is a chronic systemic autoimmune disease characterized by a broad spectrum of clinical features. It is considered to be associated with immune cells and genetic. Since the pathogenesis of pSS has not been studied thoroughly enough, it is significant to explore the relevant mechanisms using bioinformatics methods.Methods: We downloaded the GSE84844, GSE66795 and GSE51092 datasets from the GEO database, and then conducted a comprehensive bioinformatics analysis including differentially expressed genes (DEGs), functional enrichment pathways and immune infiltration characteristics. Results：DEGs analysis identified a total of 89 up-regulated genes and 11 down-regulated genes in the dataset. These DEGs were enriched in NOD-like and RIG-I-like receptor signaling pathway, which were significantly associated with the expression of immune cells such as neutrophils and activated dendritic cells, respectively.Conclusion: The NOD-like and RIG-I-like receptor signaling pathway and the pathogenesis of pSS may be closely associated. Neutrophils and dendritic cells also play an important role in pSS, and the expression of these two kinds of cells is closely associated with the signaling pathways of NOD-like and RIG-I-like receptors.

scholarly journals Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Haixiong Lin ◽  
Xiaotong Wang ◽  
Ligang Wang ◽  
Hang Dong ◽  
Peizhen Huang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Protein Targets ◽  
Pathway Enrichment ◽  
Vegf Signaling ◽  
Synergistic Mechanism

Background. Drynariae Rhizoma (DR) has been widely used in the prevention and treatment of various fractures. However, the specific mechanisms of DR’s active ingredients have not been elucidated. The purpose of this study was to explore the synergistic mechanisms of DR for treating fracture. Methods. A network pharmacology approach integrating ingredient screening, target exploration, active ingredients-gene target network construction, protein-protein interaction network construction, molecular docking, gene-protein classification, gene ontology (GO) functional analysis, KEGG pathway enrichment analysis, and signaling pathway integration was used. Results. This approach identified 17 active ingredients of DR, interacting with 144 common gene targets and 143 protein targets of DR and fracture. NCOA1, GSK3B, TTPA, and MAPK1 were identified as important gene targets. Five most important protein targets were also identified, including MAPK1, SRC, HRAS, RXRA, and NCOA1. Molecular docking found that DR has a good binding potential with common protein targets. GO functional analysis indicated that common genes involve multiple processes, parts and functions in biological process, cellular component, and molecular function, including positive regulation of transcription from RNA polymerase II promoter, signal transduction, cytosol, extracellular exosome, cytoplasm, and protein binding. The KEGG pathway enrichment analysis indicated that common gene targets play a role in repairing fractures in multiple signaling pathways, including MAPK, PI3K/AKT, Ras, and VEGF signaling pathways. MAPK and PI3K/AKT signaling pathways were involved in osteoblast formation, Ras signaling pathway was involved in enhancing mesenchymal stromal cell migration, and VEGF signaling pathway was involved in angiogenesis. Conclusion. The study revealed the correlation between DR and fracture and the potential synergistic mechanism of different targets of DR in the treatment of fractures, which provides a reference for the development of new drugs.

scholarly journals A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

2017 ◽  
Vol 27 (2) ◽  
pp. 57-69 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Olga Yu. Bushueva ◽  
Irina V. Bulgakova ◽  
Maxim B. Freidin ◽  
Mikhail I. Churnosov ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway
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